Symposium on the 3Rs

The joint NC3Rs and Society of Biology symposium held in London on Wednesday brought together researchers from disparate fields to share their work in replacing, refining and reducing the use of animals in research.

The day kicked off with a focus on maximising the information we can get from mouse models. Jacqui White described the work of the International Mouse Phenotyping Consortium who have created a systematic approach to describe the phenotypes of knockout mice. Detecting and describing changes in mice missing a gene is difficult and can be subjective, so it is hoped that their system will reduce variation in the reported descriptions. They are aiming to describe 20,000 mouse genes by 2021 and create an easy-to-use database for researchers to access.

Sara Wells from MRC Harwell spoke on efficient strategies in mice breeding, which has become hugely important since the advent of genetic engineering. She also highlighted the problem of genetic drift in mice populations, with 114 random mutations being introduced naturally with each generation. While in most cases these will have little effect on the mice, it is something that researchers must consider and mitigate where possible.

Concluding the first session, Mark Lythgoe described his work using high-resolution MRI to study mice, avoiding the need for histology and reducing the number of mice required. The technique is even sensitive enough to observe a hole the width of a human hair in the heart of mice embryos.

The second half of the day covered minimising the use of mouse models by replacing them with alternative models and techniques. These ranged from using slime moulds to study the activity of epilepsy drugs to using zebrafish larvae to understand inflammation. One of the highlights of the session was Philip Maini, director of the Centre for Mathematical Biology, who translated between the language used by biologists and mathematicians (“when a cell divides it becomes two, but to mathematicians when you divide one it becomes a half”). He stressed the importance of feedback between in vivo experiments and mathematical models, with each informing and improving the other. As an example, he highlighted his work on mathematical models of neural crest cell movement. The simulations identified that there must be different types of cells involved, which was then confirmed by experiment and the data from the experiment was fed back into simulations to gain further insights.

Describing the challenges of working with human tissue, Gareth Sanger from Queen Mary University of London finished off the day with his work on the motilin hormone. He showed that this particular hormone is missing in mice and so it is worth working on human tissue despite the variation in the lifestyles and ages of the patients that the samples come from. Human tissue has advantages, like larger samples and greater relevance to the clinic, but getting hold of tissue requires a lot of coordination from getting patients’ consent to the surgeons preserving the sample, approval from the pathologist and reaching the lab while it is still fresh.

While many of the cases presented are only suited to specific studies and would be difficult to be applied more widely, technological improvements are making it easier to replace and reduce the use of animals in more and more situations. The research posters presented at the symposium highlighted some of these, including the creation of more realistic cell cultures of human heart, lung and skin tissues. There are great range of approaches that are being developed and as these alternatives become more sophisticated scientists will be able reduce the need for animals in research, which we can all look forward to.